Merck Manual

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Opioid Analgesics

Opioid Analgesics

Drug

Adult Dose*

Pediatric Dose†

Comments

Opioid agonists in combination products‡ for moderate pain

Codeine

Oral: 30–60 mg every 4 hours

0.5–1 mg/kg

Less potent than morphine

Hydrocodone

Oral: 5–10 mg every 4–6 hours

0.135 mg/kg

More potent than codeine

Opioid agonists for moderate-to-severe pain

Fentanyl

Transdermal: 12 or 25 mcg/hour every 3 days

Transmucosal: 100–200 mcg every 2–4 hours

Intranasal: 100–200 mcg every 2–4 hours

Parenteral: 25–100 mcg every 30–60 minutes IV or as patient-controlled analgesia

Transmucosal: 5–15 mcg/kg

Parenteral: 0.5–1.0 mcg/kg

May trigger less histamine release and thus may cause less hypotension than other opioids

Transdermal: When used in cachexic patients, may result in erratic absorption and blood levels

Supplemental analgesia required at first because peak analgesia does not occur until 18–24 hours after application

May take many hours for adverse effects to resolve after removing patch

Short-acting transmucosal and intranasal forms: Used for breakthrough pain in opioid-tolerant adults and for conscious sedation in children

IV form: Sometimes used for procedural sedation

Hydromorphone

Oral tablets: 2–4 mg every 4–6 hours

Oral liquid: 2.5–10 mg every 4–6 hours

Parenteral: 0.2–1 mg every 4–6 hours or as patient-controlled analgesia

Extended-release: 8–32 mg every 24 hours

Rectal: 3 mg every 6–8 hours

Short half-life

Rectal form: Used at bedtime

Levorphanol

Oral: 2 mg every 6–8 hours

Parenteral: 2 mg every 6–8 hours

Long half-life

Meperidine

Oral: 50–300 mg every 4 hours

Parenteral: 50–150 mg every 4 hours

1.1–1.75 mg/kg

Not preferred because its active metabolite (normeperidine) causes dysphoria and central nervous system excitation (eg, myoclonus, tremulousness, seizures) and accumulates for days after dosing is begun, particularly in patients with renal failure; no longer used in some practices because of these risks

Methadone

Oral: 2.5–10 mg every 6–8 hours

Parenteral: 2.5–5 mg every 6–8 hours

Establishment of a safe, effective dose for analgesia complicated by its long half-life (usually much longer than duration of analgesia)

Requires close monitoring for several days or more after amount or frequency of dose is increased because serious toxicity can occur as the plasma level rises to steady state

Risk of QT-interval prolongation; ECG monitoring recommended

Morphine

Oral immediate-release: 10–30 mg every 4 hours

Oral controlled-release: 15 mg every 12 hours

Oral sustained-release: 30 mg every 24 hours

Parenteral: 5–10 mg every 4 hours or as patient-controlled analgesia

0.05–0.2 mg/kg every 4 hours

Standard of comparison

Triggers histamine release more often than other opioids, causing itching

Oxycodone

Oral: 5–10 mg every 6 hours

Oral controlled-release: 10–20 mg every 12 hours

Also in combination products containing acetaminophen or aspirin

Oxymorphone

Oral: 5 mg every 4 hours

Oral controlled-release: 5–10 mg every 12 hours

IM or subcutaneously: 1–1.5 mg every 4 hours

IV: 0.5 mg every 4 hours

Rectal: 5 mg every 4–6 hours

May trigger less histamine release than other opioids

Opioid agonist-antagonists§

Buprenorphine

IV or IM: 0.3 mg every 6 hours

Sublingual: 2 mg every 12 hours

Transdermal patch: 5–20 mcg/hours applied once a week (in European Union, doses may exceed 20 mcg/hour)

Use only in patients > 13 years (same as adult dose)

Psychotomimetic effects (eg, delirium, sedation) less prominent than those of other agonist-antagonists, but other effects similar

Lower risk of respiratory depression with buprenorphine than with traditional analgesics (eg, morphine, fentanyl) but not fully reversible with naloxone

Higher affinity for mu receptors than traditional analgesics

May induce acute withdrawal if added to long-term opioid therapy

Analgesic effect of traditional analgesics possibly limited when they are added to long-term therapy with buprenorphine

Butorphanol

IV: 1 (0.5–2) mg every 3–4 hours

IM: 2 (1–4) mg every 3–4 hours

Nasal: 1 mg (1 spray), repeated in 1 hour as needed

Not recommended

2-dose nasal sequence, repeated every 3–4 hours if needed

Nalbuphine

Parenteral: 10 mg every 3–6 hours

Not recommended

Psychotomimetic effects less prominent than those of pentazocine but more prominent than those of morphine; 2.5–5 mg IV (lower dose) possibly useful for pruritis (may repeat dose once)

Pentazocine

Oral: 50–100 mg every 3–4 hours

Parenteral: 30 mg every 3–4 hours (not to exceed 360 mg/day)

Not recommended

Usefulness limited by the following:

  • Ceiling effect for analgesia at higher doses

  • Potential for opioid withdrawal in patients physically dependent on opioid agonists

  • Risk of psychotomimetic effects, especially for nontolerant, nonphysically dependent patients with acute pain

Available in tablets combined with naloxone, aspirin, or acetaminophen

Can cause confusion and anxiety, especially in older patients

Mu-opioid agonists/norepinephrine reuptake inhibitors

Tapentadol

Oral immediate-release: 50 to 100 mg every 4 to 6 hours, a second dose ≥ 1 hour later (≤ 700 mg total dose on 1st day); After 1st day, 50 to 100 mg every 4 to 6 hours (≤ 600 mg total daily dose)

Oral extended-release: 50 mg every 12 hours (usual therapeutic dose of 100 to 250 mg every 12 hours; maximum 500 mg/day)

Used to treat neuropathic pain due to diabetes, moderate to severe acute pain, and moderate to severe chronic pain

Tramadol

Oral immediate-release: 50 to 100 mg every 4 to 6 hours; maximum 400 mg/day

Oral extended-release: 100 mg once a day; increase by ≤ 100 mg/day every 5 days to a dose of ≤ 300 mg total daily dose

Not recommended

Less potential for abuse than with other opioids

Not as potent as other opioid analgesics

* Starting doses are for opioid-naive patients. Patients with opioid tolerance or severe pain may require higher doses.

† Not all drugs are appropriate for analgesia in children.

‡ These opioid agonists may be combined into a single pill with acetaminophen, aspirin, or ibuprofen. They are often used alone so that acetaminophen, aspirin, or ibuprofen dosing limits do not limit opioid dosing. If combination therapy is desired, acetaminophen, aspirin, or ibuprofen can be added separately while maximizing flexibility in dosing the opioid agonist.

§ Opioid agonist-antagonists are not usually used for chronic pain and are rarely drugs of choice for older patients.